CBE & MSE Seminar: Leveraging Nobel Laureate Arthur Ashkin’s Discovery of Optical Tweezers to Probe the Cell-tissue Interface

Abstract: Matrix stiffness is a well-established instructive cue in 2D cell cultures. Understanding roles of stiffness within 3D models during processes such as morphogenesis, and the converse effects cells have on the mechanical properties of their surrounding is a major challenge. This challenge arises from the lack of suitable methods to quantify matrix stiffness on a length-scale relevant for individual cell-extracellular matrix (ECM) interactions within a 3D construct. In our study, we apply traditional bulk rheology and optical tweezers-based active microrheology to probe mechanical properties across length scales during the complex multicellular process of capillary morphogenesis in 3D. We further characterize the relative contributions of neovessels and supportive stromal cells to dynamic changes in stiffness over time. Our data show local ECM stiffness was highly heterogeneous around sprouting capillaries and the variation progressively increased with time. Both endothelial cells and stromal support cells progressively stiffened the ECM, with the changes in bulk properties dominated by the latter. Interestingly, regions with elevated stiffness values did not necessarily correlate with remodeled regions of high ECM density as shown by confocal reflectance microscopy. Collectively, these findings, especially the large spatiotemporal variations in local stiffness around cells during morphogenesis in soft 3D fibrin gels, underscore that characterizing ECM mechanics across length scales is imperative and provides an opportunity to attain a deeper mechanobiological understanding of the microenvironment's roles in cell fate and tissue patterning.

Bio: Elliot Botvinick is a professor of biomedical engineering and surgery at UC Irvine. His research program has two areas of focus, one in mechanobiology and the other in medical device development. His laboratories are located within the Edwards Lifesciences Center for Advanced Cardiovascular Technology and the Beckman Laser Institute and Medical Clinic. In general, both the mechanobiology and medical device efforts utilize photonics tools such as nonlinear microscopy, optical tweezers, luminescent reporters and laser induced cavitation. The laboratory also develops state-of-the-art instrumentation and devices for quantitative biophysical measurements toward the study of mechanobiology. These tools are applied to test mechanical hypotheses in the areas of cancer biology, microvascular morphogenesis, tissue engineering and stem cell biology. Botvinick co-founded Metronom Health, Inc, which manufactures a fiber-type transcutaneous continuous glucose monitor. The Botvinick laboratory is currently funded by the Juvenile Diabetes Research Foundation to: (1) develop a novel device for the transplantation of pancreatic or stem cells for the treatment of Type 1 diabetes, (2) develop sensors of additional signals for the artificial pancreas, including a continuous insulin monitor,  and (3) develop and test a new material to extend the lifetime of insulin infusion sets. Currently his laboratory technologies are involved in three clinical studies.

Host: Alon Gorodetsky